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Poster display

1618 - Tyrosine kinase inhibitors targeted therapy and the AKT-m-TOR pathway in kidney cancer tissues

Date

10 Oct 2016

Session

Poster display

Presenters

Liudmila Spirina

Citation

Annals of Oncology (2016) 27 (6): 545-551. 10.1093/annonc/mdw393

Authors

L.V. Spirina1, E. Usynin2, I. Kondakova1, Z. Yurmazov2, E. Slonimskaya3, E. Kolegova1

Author affiliations

  • 1 Laboratory Of Tumor Biochemistry, Tomsk Cancer Research Institute RAMS, 634050 - Tomsk/RU
  • 2 Oncology, Tomsk Cancer Research Institute, 634050 - Tomsk/RU
  • 3 Department Of General Oncology, Tomsk Cancer Research Institute RAMS, 634050 - Tomsk/RU
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Abstract 1618

Background

Modifications of molecular features by the action of tyrosine kinase inhibitors (TKIs) in tumors are the basis of anticancer treatment efficacy. The aim of the study is investigation of AKT-m-TOR pathway components in kidney cancer tissues before and after TKI-targeted therapy.

Methods

The study included 30 patients with metastatic clear cell kidney cancers. The treatment of these men consisted of pre-operational sorafinib targeted therapy in dose of 400 mg every day during the two months. Then the radical nephrectomy was performed. Content of phospho-PTEN, AKT (pan), phospho-AKT (T308), phospho-AKT (S473), phospho-GSK-3-beta (Ser9), phospho-PDK1 (Ser241), phospho-c-Raf (Ser259), m-TOR, phospho-mTOR (Ser2448), phospho-p70 S6 (Ser371), phospho-p70 S6 (T389) phospho-4E-BP1 (Thr37/46) was determined by western blotting analysis in tissues before and after targeted therapy.

Results

We have revealed the increased content of total AKT (pan), phospho-GSK-3-beta, phospho-PDK1, phospho-c-Raf in 91.0; 67.4; 46.0% and 69.0% in cancer tissues, respectively, compared with unaltered ones. The m-TOR, its phosphorylated form and phospho-4E-BP1 in kidney cancers were increased 76.1%; 67.2% and 78.7%, respectively, in comparison to normal tissues. We found the reduced level of phospho-PTEN in 1.7 fold after treatment. It was also noted that the decrease in the amount of phosphorylated AKT (T308) was 1.5-fold compared with that before the treatment. The phospho-p70 S6 (S371) kinase expression was increased 1.9-fold in patients receiving TKI-targeted therapies.

Conclusions

TKI-targeted therapy was associated with the reduction of AKT signaling pathway activation. The fall of PTEN and gain of p70 S6 kinase levels during treatment were observed Acknowledgments.

Clinical trial identification

Legal entity responsible for the study

Tomsk Cancer Research Institute

Funding

President Grant №MD-3637.2015

Disclosure

All authors have declared no conflicts of interest.

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